Objective To evaluate the efficacy and safety in treatment of patients with mild to moderate Alzheimer’s disease (AD). Methods A total of 233 patients with mild to moderate potential AD were enrolled in a 16-week multi-center double blind clinical trial. All patients were randomized into two groups. 110 patients in galantamine group and 108 patients in donepezil group were enrolled in efficacy analysis. The scales of Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale (ADCS-ADL) and The Neuropsychiatric Inventory (NPI) were used to assess the effect at both baseline and the end of 16 weeks. Safety issues, including vital signs, lab assays and ECG examinations were measured. Results Patients in both groups were obviously improved in the total score of ADAS-cog (-5.4?6.4) in the galantamine group and (-4.0?7.3) in the donepezil group, P=0.098). 76% patients of the galantamine group had a score of ADAS-cog less than 20 at the end of 16 weeks treatment, which was higher than that of the donepezil group (58%, P=0.015). The sub-score of speech ability in ADAS-cog were improved in the galantamine group (baseline 2.8?2.9,16 weeks 1.8?2.5) compared with the donepezil group (baseline 2.8?3.0, 16 weeks 2.3?2.9, P=0.035). No significant difference of ADSC-ADL and NPI scale was found between the two groups (P=0.447 and 0.936 respectively). The sleep/night behavior was improved in the donepezil group (baseline 14%, 16 weeks 10%) compared with the galantamine group (baseline 23%, 16 weeks 22%, P=0.012). Two drug-related severe adverse events occurred during the trial, which were platelet reduction in the galantamine group and acute drug-induced hepatic injury in the donepezil group. The incidence of adverse events was 44% in the galantamine group and 47% in the donepezil group respectively. Galantamine had little influence on vital signs and lab assays. Conclusion Safe and well tolerated, galantamine improves the cognition, activities of daily living and neuropsychiatric symptoms of patients with mild to moderate AD.

Objective To introduce the tibial intercondylar eminence hole (TIEH) and study its structure.Explore the connection between TIEH and the pathway how proximal tibial aggressive tumor break into the bony structure from articular cavity.Methods This retrospective study included 200 patient's CT 3-dimensional reconstruction materials from May 2017 to November 2017 in Qilu hospital randomly.There were 115 males and 85 females,the average age was 49 years (ranged from 12 to 90 years).To observe the existence of TIEH and identify its location and measurement with imaging techniques.According to 50 tibial plateau specimen after TKA and 5 specimen after car accident or amputation due to tumor,physical proof the existence of TIEH.The specific location,peripheral structure,coverage,content of TIEH as well as its top,walls and bottom were researched and analysed.Pathological staining was used and 1 cases undertook preoperation contrast agent observation.1 cases of typical cases were reviewed.Results TIEH was ubiquity according to all of the 200 cases.TIEH was located on the depression of tibial plateau,between the attachments of ACL and PCL.The hole was round type,and the diameter was 1.6±0.3 mm,the depth was 9.1±2.1 mm.1-3 Paraforamen (semidiamete≤7 mm) were found around the main TIEH in 53％ patients (106/200),the diameter and depth was less than the main hole.The CT value showed the orifice (472.5±30.1 HU) ＞ the pore wall (312.3±22.5 HU) ＞ the pore bottom (202.4±17.3 HU) ＞ the pore (118.3±10.4 HU) ＞ the orifice covering (75.0±11.1 HU).The synovial tissue septum was only 1 mm between the top of hole and the articular cavity.The top of TIEH was surrounded by articular cartilage,the walls and bottom were spongy bone,the content was dense connective tissue that didn't attach to the walls tightly.The peripheral spongy bone was easy to infiltrate by methylene blue.Preoperation radiography showed that TIEH had poor barrier function.Conclusion Tibial intercondylar eminence hole is an intrinsic structure of the human body.The coverage is weak,and it is easy to cause the tumor to hide and recur.The tumor may pass through this hole and bidirectionally enter between the proximal humerus and the joint cavity.

Objective:To introduce the discovery and nomenclature of the intercondylar foramen of femur (IFF) and foramen of tibial intercondylar eminence (FTIE) and research the close relationship between the high recurrence rate of aggressive tumors around the knee joint and the foramina around the knee joint.Methods:①Radiographic observation and measurement: 3D reconstruction of CT scan of 200 patients in our hospital were used to obverse the common feature、position and measure of Inter-condylar foramen of femur and Foramen of tibial intercondylar eminence. ②Anatomical and histological observation: To proof the existence of IFF and FTIE through the anatomy of 15 cases of car accidents or tumor amputations and 60 cases of autopsy. Then the specific location, the surrounding structure, the proximal coverage, the contents, the apical construction, the wall and the bottom tissues of the IFF and FTIE were studied and analyzed. ③Histological and pathological observation of tumor anatomy: Through the study of the distal femur and tibia malignant tumor tissues(including primary bone tumors and metastatic tumors), we observed the relationship between the foraminal structures and the tumor, judged the situation of concealed transmission and two-way spread through the foramina, and analyzed the relationship between tumor recurrence and foraminal structures. ④The synovial membrane of foramina, especially in cases where the synovium was suspected to be involved by the lesions judged by the radiography was analyzed to observe whether the synovium was infiltrated by the tumor.Results:IFF and FTIE were the inherent physical structure of the human. Their physiological function was the vascular foramina that lead the branches of arteria media genus into the Intercondylar fossa of femur and tibial intercondylar eminence. Their opening was separated with the joint cavity by the synovial tissues, so IFF and FTIE were isolated with joint cavity by the synovial tissues、meniscus and cruciate ligaments. After invading the IFF and FTIE, the aggressive tumors did not break into the joint cavity immediately, but conceal in the foramina and invade the synovium with specific biological behavior with the sequence: reactive edema, hyperplasia, degeneration, calcification, hyaline degeneration (infiltration in some cases), synovial rupture, and then tumor invasion of the articular cavity. Usually, tumors or recurrence has been observed before synovial rupture. We also observed the tendency of tumors to spread along the arteria media genus to the popliteal vessels, peripheral soft tissues and lymphatic vessels with typical radiographic performance like popliteal lymphadenectasis. Color nodules and tumors in other parts could also invade or metastasize into bone through these foramina.Conclusions:IFF and FTIE are foramina nutricium of arteria media genus. They are the inherent physical structure of the human. The foramina play an important role in the spread, concealment and recurrence of peripheralkneeaggressive tumor.

Objective:The vasculature and canal were located using radiography after the fresh osseous specimens were decalcified, after which the anatomic investigation of intraosseous vasculature was conducted based on the orientation of the canals.Methods:To investigate the basic dissected methods for intraosseous vasculature and the related clinical significance. Methods The materials were obtained from seven fresh knee joint specimens from patients with amputation due to car accidents, nine fresh knee joint specimens from patients with amputation due to oncological radical surgery, and 44 knee joint specimens from 24 cadavers. Among them, 22 were males (55%) and 18 were females (45%), 28 were left knees (46.7%) and 32 were right knees (53.3%). 10 were aged from 16-90 years old (from 8 donors) and 50 were aged from 15-85 years old (from 32 donors). The tributaries of middle genicular vein which penetrate into the proximal tibial epiphysis and metaphysis via our previously discovered and denominated "foramen of tibial intercondylar eminence (FTIE)" were dissected as an example. After obtaining the fresh knee joint specimen, angiography was performed to observe the continuous extraosseous and intraosseous blood vessels. The first group of specimens with the removal of cortical bone was reserved in formalin solution at 4 °C for 7 d, sequentially immersed in Ethylene Diamine Tetraacetic Acid (EDTA), the decalcification agent, for 30 d with replacement for each two days. Based on the CT scanning and three-dimensional reconstruction, the orientation of bony canal which enclosed the vasculature was exposed to guide the anatomic incision. The exquisite dissection was achieved with the help of ophthalmological microsurgical instruments. The anatomical dissection were intuitively observed, compared with the angiographic images, and verified by histological examinations. The second group of samples was decalcified with strong acid as another strategy, and the comparison between different groups was conducted. To estimate the advantages and disadvantages of the two decalcification and dissection methods, and the distribution and universality of specific intraosseous vasculatures and canals, the methods can be utilized to dissect the diameter of the intraosseous vessels. Based on the anatomical study of intraosseous vasculature, the mechanisms including etiology, recurrence and spread of bone tumors and epiphyseal injuries were analyzed to improve the therapeutic regimen.Results:The intraosseous tributaries of middle genicular vein which penetrate into the tibial intercondylar eminence from the articular cavity were dissected, these vessels extended to the tibial metaphysis from epiphysis through the epiphyseal line or senescent physes. The diameter of the vessel entering the FTIE was 1.2 mm, and the intraosseous vessels divided into several tinier tributaries with the diameter of 0.3 mm to cross the epiphyseal line or closed physeal plate and differentiated into capillaries in the distal regions, therefore was difficult to dissect directly. The histological examinations confirmed the authenticity of intraosseous vessels. Compared with the samples decalcified with strong acid, the blood vessels were obviously dissolved, and only a few residual epithelial cells were observed under the light microscope. Based on the anatomical study of intraosseous vessels, the treatment protocols for some related bone tumors and epiphyseal injuries were modified and satisfactory results were achieved.Conclusion:The methods can realize the ideal direct dissection for the intraosseous blood vessels with the outer diameter greater than or equal to 0.3 mm.